5-(1-hydroxy-3-methylbutylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione | 146380-12-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(1-hydroxy-3-methylbutylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
• 英文别名: 2,2-dimethyl-5-(1-hydroxy-3-methyl-butyryl)-[1,3]dioxane-4,6-dione
• CAS: 146380-12-3
• 化学式: C₁₁H₁₆O₅
• 分子量: 228.245
• InChiKey: MCZWCBVHAVUVLR-UHFFFAOYSA-N

物化性质

• 沸点：
  400.0±42.0 °C(Predicted)
• 密度：
  1.184±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(1-hydroxy-3-methylbutylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 以 乙醇 为溶剂， 生成 5-甲基-3-羰基己酸乙酯
  参考文献：
  名称：

  Modulators of calcitonin and amylin receptor activity

  摘要：

  在各个方面，本发明涉及调节降钙素和淀粉样蛋白样受体活性的非肽类化合物；制备这类化合物的方法；以及包括这类化合物的药物组合物。本发明的化合物可用作降钙素和/或淀粉样蛋白样受体激动剂，并用于治疗骨疾病和代谢性疾病。

  公开号：

  US07396936B1
• 作为产物：
  描述：

  丙二酸环(亚)异丙酯 、 异戊酰氯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 5-(1-hydroxy-3-methylbutylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
  参考文献：
  名称：

  发现3-吡啶基乙酸衍生物（TAK-100）作为有力，选择性和口服活性的二肽基肽酶IV（DPP-4）抑制剂

  摘要：

  抑制二肽基肽酶IV（DPP-4）是治疗糖尿病的令人兴奋的新方法。迄今为止，尚无具有羧基的DPP-4化学型已进入临床试验。从发现结构新颖的喹啉衍生物1出发，我们设计了含有羧基的新型吡啶衍生物。在我们的设计中，羧基与催化区域周围的目标氨基酸残基相互作用，从而增加了抑制活性。经过进一步优化后，我们确定了[5-（氨基甲基）-6-（2,2-二甲基丙基）-2-乙基-4-（4-甲基苯基）吡啶-3-基]乙酸的水合物（30c）作为有效且选择性的DPP-4抑制剂。通过X射线共晶结构分析确认了与关键活性位点残基的所需相互作用，例如与Arg125的盐桥相互作用。此外，化合物30c表现出所需的临床前安全性，编码为TAK-100。

  DOI：

  10.1021/jm101236h

文献信息

• Microwave-Assisted Solution-Phase Synthesis of 1,4,5-Trisubstituted Pyrazoles
  作者：Giampaolo Giacomelli、Andrea Porcheddu、Margherita Salaris、Maurizio Taddei

  DOI：10.1002/ejoc.200390091

  日期：2003.2

  A small parallel library of 1,4,5-trisubstituted pyrazoles was prepared in solution using a three-step procedure starting from Meldrum acid. The Meldrum acid was acylated with different acyl chlorides and the products opened with different alcohols and amines to give substituted β-keto esters and β-keto amines. Further reaction with N,N-dimethylformamide dimethylacetal and the final cyclisation were

  使用三步法从 Meldrum 酸开始，在溶液中制备了一个小型的 1,4,5-三取代吡唑平行库。Meldrum酸用不同的酰氯酰化，产物用不同的醇和胺打开，得到取代的β-酮酯和β-酮胺。与 N,N-二甲基甲酰胺二甲基缩醛的进一步反应和最终的环化在微波辐射下有效地进行。在第一步中仅使用清除剂树脂，而在其他两个步骤中使用微波可以使起始材料完全转化。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
• [EN] COMPOSITIONS AND METHODS FOR ADJUVANT CANCER THERAPEUTICS<br/>[FR] COMPOSITIONS ET MÉTHODES POUR LE TRAITEMENT ADJUVANT DU CANCER
  申请人：UNIV DUKE

  公开号：WO2020077014A1

  公开（公告）日：2020-04-16

  This invention relates to compounds, pharmaceutical compositions comprising them, and methods of using the compounds and compositions for treating diseases related to translesion synthesis (TLS) pathway. More particularly, this disclosure relates to small molecule inhibitors of TLS, methods of inhibiting TLS pathway with these compounds, and methods of treating diseases related to the TLS pathway.

  本发明涉及化合物、包含它们的药物组合物以及使用这些化合物和组合物治疗与转录后修复（TLS）途径相关的疾病的方法。更具体地，本公开涉及TLS的小分子抑制剂，使用这些化合物抑制TLS途径的方法，以及治疗与TLS途径相关疾病的方法。
• Aminolysis of 5-Acyl-2,2-dimethyl-1,3-dioxane-4,6-diones (Acyl Meldrum's Acids) as a Versatile Method for the Synthesis of β-Oxo Carboxamides
  作者：Chwang Siek Pak、Heui Cheol Yang、Eun Bok Choi

  DOI：10.1055/s-1992-26338

  日期：——

  5-Acyl-2,2-dimethyl-1,3-dioxane-4,6-diones (acyl Meldrum's acids) underwent aminolysis with various amines to afford the corresponding ß-oxo carboxamides in high yields.

  5-酰基-2,2-二甲基-1,3-二恶烷-4,6-二酮（酰基梅尔德鲁姆酸）与各种胺发生氨解反应，可以高产率得到相应的 ß-氧代羧酰胺。
• 3-Oxoisoxazole-2(3H)-carboxamides and isoxazol-3-yl carbamates: Resistance-breaking acetylcholinesterase inhibitors targeting the malaria mosquito, Anopheles gambiae
  作者：Astha Verma、Dawn M. Wong、Rafique Islam、Fan Tong、Maryam Ghavami、James M. Mutunga、Carla Slebodnick、Jianyong Li、Elisabet Viayna、Polo C.-H. Lam、Maxim M. Totrov、Jeffrey R. Bloomquist、Paul R. Carlier

  DOI：10.1016/j.bmc.2015.01.026

  日期：2015.3

  To identify potential selective and resistance-breaking mosquitocides against the African malaria vector Anopheles gambiae, we investigated the acetylcholinesterase (AChE) inhibitory and mosquitocidal properties of isoxazol-3-yl dimethylcarbamates (15), and the corresponding 3-oxoisoxazole-2(3H)-dimethylcarboxamide isomers (14). In both series, compounds were found with excellent contact toxicity to wild-type susceptible (G3) strain and multiply resistant (Akron) strain mosquitoes that carry the G119S resistance mutation of AChE. Compounds possessing good to excellent toxicity to Akron strain mosquitoes inhibit the G119S mutant of An. gambiae AChE (AgAChE) with k(i) values at least 10-to 600-fold higher than that of propoxur, a compound that does not kill Akron mosquitoes at the highest concentration tested. On average, inactivation of WT AgAChE by dimethylcarboxamides 14 was 10-20 fold faster than that of the corresponding isoxazol-3-yl dimethylcarbamates 15. X-ray crystallography of dimethylcarboxamide 14d provided insight into that reactivity, a finding that may explain the inhibitory power of structurally-related inhibitors of hormone-sensitive lipase. Finally, human/An. gambiae AChE inhibition selectivities of these compounds were low, suggesting the need for additional structural modification. (C) 2015 Elsevier Ltd. All rights reserved.
• COMPOSITIONS AND METHODS FOR ADJUVANT CANCER THERAPEUTICS
  申请人：DUKE UNIVERSITY

  公开号：US20220008408A1

  公开（公告）日：2022-01-13

  This invention relates to compounds, pharmaceutical compositions comprising them, and methods of using the compounds and compositions for treating diseases related to translesion synthesis (TLS) pathway. More particularly, this disclosure relates to small molecule inhibitors of TLS, methods of inhibiting TLS pathway with these compounds, and methods of treating diseases related to the TLS pathway.